The present invention relates to a method of determining the autoregulatory status of a subject. More specifically, the present invention relates to a method for measuring the autoregulatory status of a subject by noninvasively monitoring blood vessel changes in the retina.
Local autoregulation is the physiologic phenomenon where the vascular bed attempts to match supply of substrate (primarily oxygen and glucose) and the removal of metabolic waste (primarily carbon dioxide and lactic acid) to the metabolic demand of the tissues by changing the resistance to flow therethrough. Resistance to flow is controlled by changes in blood vessel wall tension which changes the diameter of the blood vessels. When supply is generous, the blood vessels constrict decreasing flow. Conversely, when supply is limited, the blood vessels dilate increasing flow. Some of the substances which are known to change the autoregulatory state of tissues include oxygen, glucose, carbon dioxide and lactic acid.
Blood supply to the tissues is regulated by chemical signals transported throughout the body by the blood, by local metabolic demand, and by the autonomic nervous system which has nerve endings traveling with the blood vessels. Circulating substances generally regulate the balance of flow to the major organ systems of the body. An example of this is when a subject is bleeding and circulating catecholamines are released which shunt blood flow from the peripheral tissues to the central organs such as the brain and heart.
The retina is an embryologic extension of the brain and, as such, it is a centrally perfused organ and would not be expected to restrict flow in response to circulating substances released to maintain flow to the central circulation. The autonomic nerve endings which travel with the blood vessels in the body stop at the lamina cribosa prior to entering the retina. This allows the retinal circulation to respond to circulating chemical regulators and to local metabolic demand without interference from the autonomic nervous system. Accordingly, this characteristic makes the retina an ideal location for studying and assessing autoregulatory states by analyzing changes in the retinal blood vessel diameter and/or oxyhemoglobin saturation.
The analysis of retinal blood vessels to diagnose autoregulatory function/dysfunction can be useful in diagnosing and treating various diseases which have an autoregulatory dysfunction as a component of the disease. Examples of such diseases include diabetes, hypertension and glaucoma.
Glaucoma accounts for between 9% and 12% of all cases of blindness in the United States. Between two and three million people aged forty and older have glaucoma, and between 89,000 and 120,000 are blind from it. Glaucoma was originally believed to be a problem of elevated intraocular pressure (IOP) causing damage to the optic nerve. It is now clear that glaucoma clinically is a heterogenous collection of disorders with a similar clinical course and presentation. There are many treatment modalities for glaucoma, yet all are designed to do only one thingxe2x80x94lower IOP. Without treatment there is a relentless course of progressive visual loss. Unfortunately, many people have continued progression even when treatment is believed to have stabilized IOP in the normal range. This finding coupled with the fact that approximately one-third of glaucoma patients have normal IOP or Normal Tension Glaucoma (NTG) has led to exploration of other etiologies, such as vascular causes. A vascular role was initially suggested because of the association of glaucoma with systemic vascular diseases such as hypertension, migraine, diabetes and peripheral vascular disease. In addition, the presence of disk hemorrhages and retinal vein occlusions early in the glaucomatous disease process supports the vascular theory.
Although research on the vascular theories of glaucoma have focused on autoregulation, many of the parameters related to the blood vessel size, shape and blood flow hemodynamics have been difficult to quantify. Color Doppler Imaging (CDI) has been used to measure the peak blood flow velocity in the ocular blood vessels. These studies have demonstrated that blood velocity is decreased in the ophthalmic artery, posterior ciliary artery and central retinal artery of glaucoma patients.
Quantification of the vascular aspects of glaucoma has been difficult due to our limited knowledge of blood flow hemodynamics and autoregulatory mechanisms in the eye. Because there is no autonomic innervation of the retinal circulation distal to the lamina cribosa, autoregulatory mechanisms in the retina are controlled locally. Several studies have concluded that autoregulation in normal patients is similar to the autoregulation in ocular hypertensive patients, but autoregulation in glaucoma patients is insufficient.
Accordingly, it would be both advantageous and desirable to have a rapid, noninvasive method for measuring the retinal autoregulatory status of a subject in order to obtain information regarding the subject""s condition which will be useful in the diagnosis and treatment of conditions having an autoregulatory component including glaucoma.